1,510 research outputs found

    Linalool, a plant-derived monoterpene alcohol, reverses doxorubicin resistance in human breast adenocarcinoma cells

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    Essential oils from various aromatic plants have been reported to exert chemopreventive and/or antitumor effects. In addition, a number of studies have shown the ability of chemopreventive phytochemicals to increase the sensitivity of cancer cells to conventional anticancer drugs. The success of chemotherapeutic agents is often hindered by the development of drug resistance, with multidrug resistant (MDR) phenotypes reported in a number of tumors, generally involving reduced intracellular drug accumulation due to increased drug efflux by membrane transporters. In the present study, the effects of linalool (LIN), a monoterpene alcohol found in the essential oils from many aromatic plants, on the growth of two human breast adenocarcinoma cell lines, MCF7 WT and multidrug resistant MCF7 AdrR, were investigated, both as a single agent and in combination with doxorubicin (DOX). The results reported here show that LIN only moderately inhibits cell proliferation; interestingly, however, subtoxic concentrations of LIN potentiate DOX-induced cytotoxicity and pro-apoptotic effects in both cell lines. A significant synergism can be observed in MCF7 AdrR cells, which may be due, at least in part, to the ability of LIN to increase DOX accumulation and to induce a decrease in Bcl-xL levels. In summary, the results of the present study suggest that LIN may improve the therapeutic index of anthracyclines in the management of breast cancer, especially in MDR tumors

    Analytical modeling of HSUPA-enabled UMTS networks for capacity planning

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    In recent years, mobile communication networks have experienced significant evolution. The 3G mobile communication system, UMTS, employs WCDMA as the air interface standard, which leads to quite different mobile network planning and dimensioning processes compared with 2G systems. The UMTS system capacity is limited by the received interference at NodeBs due to the unique features of WCDMA, which is denoted as `soft capacity'. Consequently, the key challenge in UMTS radio network planning has been shifted from channel allocation in the channelized 2G systems to blocking and outage probabilities computation under the `cell breathing' effects which are due to the relationship between network coverage and capacity. The interference characterization, especially for the other-cell interference, is one of the most important components in 3G mobile networks planning. This monograph firstly investigates the system behavior in the operation of UMTS uplink, and develops the analytic techniques to model interference and system load as fully-characterized random variables, which can be directly applicable to the performance modeling of such networks. When the analysis progresses from single-cell scenario to multi-cell scenario, as the target SIR oriented power control mechanism is employed for maximum capacity, more sophisticated system operation, `feedback behavior', has emerged, as the interference levels at different cells depend on each other. Such behaviors are also captured into the constructed interference model by iterative and approximation approaches. The models are then extended to cater for the features of the newly introduced HSUPA, which provides enhanced dedicated channels for the packet switched data services such that much higher bandwidth can be achieved for best-effort elastic traffic, which allows network operators to cope with the coexistence of both circuit-switched and packet-switched traffic and guarantee the QoS requirements. During the derivation, we consider various propagation models, traffic models, resource allocation schemes for many possible scenarios, each of which may lead to different analytical models. All the suggested models are validated with either Monte-Carlo simulations or discrete event simulations, where excellent matches between results are always achieved. Furthermore, this monograph studies the optimization-based resource allocation strategies in the UMTS uplink with integrated QoS/best-effort traffic. Optimization techniques, both linear-programming based and non-linear-programming based, are used to determine how much resource should be assigned to each enhanced uplink user in the multi-cell environment where each NodeB possesses full knowledge of the whole network. The system performance under such resource allocation schemes are analyzed and compared via Monte-Carlo simulations, which verifies that the proposed framework may serve as a good estimation and optimal reference to study how systems perform for network operators

    Chronic mild stress-induced alterations of clock gene expression in rat prefrontal cortex: modulatory effects of prolonged lurasidone treatment

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    Disruptions of biological rhythms are known to be associated with depressive disorders, suggesting that abnormalities in the molecular clock may contribute to the development of these disorders. These mechanisms have been extensively characterized in the suprachiasmatic nucleus, but little is know about the role exerted by individual clock genes in brain structures that are important for depressive disorders. Using the chronic mild stress model we found a significant reduction of BMAL1 and CLOCK protein levels in the nuclear compartment of the prefrontal cortex of CMS rats, which was paralleled by a down-regulation of the expression of several target genes, including Pers and Crys but also Reverb\u3b2 and Ppar\u3b1. Interestingly, chronic treatment with the multi receptor modulator lurasidone (3 mg/kg for 5 weeks) was able to normalize the molecular changes induced by CMS exposure in prefrontal cortex, but it was also able to regulate some of these genes within the hippocampus. We believe that changes in clock genes expression after CMS exposure may contribute to the disturbances associated with depressive disorders and that the ability of chronic lurasidone to normalize such alterations may be relevant for its therapeutic properties in ameliorating functions that are deteriorated in patients with major depression and other stress-related disorders

    Structural relaxations in electronically excited poly(para-phenylene)

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    Structural relaxations in electronically excited poly(para-phenylene) are studied using many-body perturbation theory and density-functional-theory methods. A sophisticated description of the electron-hole interaction is required to describe the energies of the excitonic states, but we show that the structural relaxations associated with exciton formation can be obtained quite accurately within a constrained density-functional-theory approach. We find that the structural relaxations in the low-energy excitonic states extend over about 8 monomers, leading to an energy reduction of 0.22 eV and a Stokes shift of 0.40 eV.Comment: 4 pages, 3 figure

    Bienestar subjetivo en la Argentina durante el período 2005-2007. Determinantes de la felicidad, según la Encuesta de la Deuda Social Argentina (EDSA)

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    This paper has as main objective to study the determinants of the self-perception of happiness in Argentina between the years 2005 and 2007, by using information gathered from the Survey of Argentina’s Social Debt (Encuesta de la Deuda Social Argentina-EDSA) carried out by the Catholic University of Argentina (Universidad Católica Argentina-UCA). The study was performed by means of a statistical-descriptive analysis and a series of multivariate econometric models of the arranged logit type that allowed to identify the perception of enough determinants having an effect on the self-perception of happiness in a positive and statistically significant way: the income; the self-perceived health status; the employment and its quality; the civil status; the quantity of children in the home; the least perceived discrimination; the communion with God; and the free time.Este artículo tiene como principal objetivo estudiar los determinantes de la autopercepción de felicidad en la Argentina entre 2005 y 2007, utilizando información de la Encuesta de laDeuda Social Argentina (EDSA) relevada por la Universidad Católica Argentina (UCA). Elestudio se lleva a cabo mediante un análisis estadístico descriptivo y una serie de modeloseconométricos multivariados de tipo logit ordenado que permitieron identificar la percepción de suficientes determinantes que afectan la autopercepción de felicidad de manera positiva y estadísticamente significativa: el ingreso; el estado de salud autopercibido; el empleo y su calidad; el estado civil; la cantidad de hijos en el hogar; la menor discriminación percibida; estar en comunión con Dios; y el tiempo libre

    Folded Radial Forearm Free Flap for the Reconstruction of Total Soft Palate Defects: Operative Technique

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    Background: The surgical plan to reconstruct the palate must be carefully prepared given the morphological peculiarity of the soft palate forming both the roof of the mouth and the floor of the nasal cavity. This article focuses on the use of folded radial forearm free flaps to manage isolated defects of the soft palate in the absence of tonsillar pillar involvement. Methods: Three patients affected by squamous cell carcinoma of the palate underwent resection of the soft palate and immediate reconstruction with a folded radial forearm free flap. Results: All three patients showed good short-term morphological-functional outcomes as far as swallowing, breathing, and phonation were concerned. Conclusions: The folded radial forearm free flap seems to be an efficacious way to manage localized defects of the soft palate, given the positive outcomes of the three patients treated, and in accordance with other authors. In general, the radial forearm free flap was confirmed to be a versatile solution for those intraoral defects of the soft tissue requiring a limited quantity of volume as in the case of the soft palate

    Structural, electronic, and dynamical properties of amorphous gallium arsenide: a comparison between two topological models

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    We present a detailed study of the effect of local chemical ordering on the structural, electronic, and dynamical properties of amorphous gallium arsenide. Using the recently-proposed ``activation-relaxation technique'' and empirical potentials, we have constructed two 216-atom tetrahedral continuous random networks with different topological properties, which were further relaxed using tight-binding molecular dynamics. The first network corresponds to the traditional, amorphous, Polk-type, network, randomly decorated with Ga and As atoms. The second is an amorphous structure with a minimum of wrong (homopolar) bonds, and therefore a minimum of odd-membered atomic rings, and thus corresponds to the Connell-Temkin model. By comparing the structural, electronic, and dynamical properties of these two models, we show that the Connell-Temkin network is energetically favored over Polk, but that most properties are little affected by the differences in topology. We conclude that most indirect experimental evidence for the presence (or absence) of wrong bonds is much weaker than previously believed and that only direct structural measurements, i.e., of such quantities as partial radial distribution functions, can provide quantitative information on these defects in a-GaAs.Comment: 10 pages, 7 ps figures with eps

    Unravelling the roles of size, ligands and pressure in the piezochromic properties of CdS nanocrystals

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    Understanding the effects of pressure-induced deformations on the optoelectronic properties of nanomaterials is important not only from the fundamental point of view, but also for potential applications such as stress sensors and electromechanical devices. Here we describe the novel insights into these piezochromic effects gained from using a linear-scaling density functional theory framework and an electronic enthalpy scheme, which allow us to accurately characterize the electronic structure of CdS nanocrystals with a zincblende-like core of experimentally relevant size. In particular we focus on unravelling the complex interplay of size and surface (phenyl) ligands with pressure. We show that pressure-induced deformations are not simple isotropic scaling of the original structures and that the change in HOMO-LUMO gap with pressure results from two competing factors: (i) a bulk-like linear increase due to compression, which is offset by (ii) distortions/disorder and, to a lesser extent, orbital hybridization induced by ligands affecting the frontier orbitals. Moreover, we observe that the main peak in the optical absorption spectra is systematically red-shifted or blue-shifted, as pressure is increased up to 5 GPa, depending on the presence or absence of phenyl ligands. These heavily hybridize the frontier orbitals, causing a reduction in overlap and oscillator strength, so that at zero pressure the lowest energy transition involves deeper hole orbitals than in the case of hydrogencapped nanocrystals; the application of pressure induces greater delocalisation over the whole nanocrystals bringing the frontier hole orbitals into play and resulting in an unexpected red shift for the phenyl-capped nanocrystals, in part caused by distortions. In response to a growing interest in relatively small nanocrystals that can be difficult to accurately characterize with experimental techniques, this work exemplifies the detailed understanding of structure-property relationships under pressure that can be obtained for realistic nanocrystals with state-of-the-art first principles methods and used for the characterization and design of devices based on these and similar nanomaterials
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